Clonal Hematopoiesis and Premalignant Diseases
Clonal Hematopoiesis and Premalignant Diseases
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DOI：
10.1101/cshperspect.a035675
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发表时间：
2020-04-01
影响因子：
5.4
通讯作者：
Hassane, Duane C.
中科院分区：
文献类型：
--
作者：
Kaner, Justin;Desai, Pinkal;Hassane, Duane C.
当造血系统中的突变赋予特定克隆以适应性优势，从而有利于它们的不成比例生长时，克隆造血（CH）出现。CH的存在随着年龄和环境暴露（如细胞毒性化疗或放疗）而增加。最常见的突变发生在表观遗传调节因子中，如DNMT3A，TET2和ASXL1，导致肿瘤抑制功能，病原体反应和炎症的失调。这些失调的过程增加了总体死亡率、心血管疾病和最终血液恶性肿瘤（HM）的风险。CHis可能充当导致HM的起始事件，随后发生协同突变。然而，进一步的证据表明，CH通过其促炎特性发挥旁观者影响。描述导致CH发病和扩展的机制以及其对HM风险的贡献对于确定管理和干预策略至关重要。在这篇综述中，我们讨论了潜在的原因，后果，技术考虑，和可能的管理策略CH的背景下，HM和前HM。
Clonal hematopoiesis (CH) arises when mutations in the hematopoietic system confer a fitness advantage to specific clones, thereby favoring their disproportionate growth. The presence of CH increases with age and environmental exposures such as cytotoxic chemotherapy or radiotherapy. The most frequent mutations occur in epigenetic regulators, such as DNMT3A, TET2, and ASXL1, leading to dysregulation of tumor suppressor function, pathogen response, and inflammation. These dysregulated processes elevate risk of overall mortality, cardiovascular disease, and eventual hematologic malignancy (HM). CHis likely acting as an initiating event leading to HM when followed by cooperating mutations. However, further evidence suggests that CH exerts a bystander influence through its pro-inflammatory properties. Delineating the mechanisms that lead to the onset and expansion of CH as well as its contribution to risk of HM is crucial to defining a management and intervention strategy. In this review, we discuss the potential causes, consequences, technical considerations, and possible management strategies for CH in the context of HMs and pre-HMs.